NCT03390595

Avelumab Plus Carboplatin-gemcitabine in Urothelial Carcinoma

Phase II Multicentre, Randomized, Open-label Study to Evaluate the Safety and Efficacy of Avelumab With Gemcitabine/Carboplatin Versus Gemcitabine/Carboplatin Alone in Patients With Unresectable or Metastatic Urothelial Carcinoma (UC) Who Have Not Received Prior Systemic Therapy and Who Are Ineligible to Receive Cisplatin-based Therapy.

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 85 (actual)
• Sponsor: Associació per a la Recerca Oncologica, Spain · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Phase II Multicentre, randomized, open-label study to evaluate the safety and efficacy of avelumab with gemcitabine/carboplatin versus gemcitabine/carboplatin alone in patients with unresectable or metastatic urothelial carcinoma (UC) who have not received prior systemic therapy and who are ineligible to receive cisplatin-based therapy.

Detailed description

The aim of this study is to evaluate if the response rates (complete response \[CR\] + partial response \[PR\]) are sufficiently high and the severe acute toxicity rates acceptably low. Patients must be cisplatin-ineligible as defined by consensus criteria (see Inclusion criteria). Patients who experience disease progression \>12 months following completion of a platinum-based adjuvant or neoadjuvant regimen will also be eligible for enrolment into the study. Once it is confirmed that the subjects fulfil the eligibility criteria and have signed the informed consent form, they will be randomized in a 1:1 ratio to receive avelumab in combination with gemcitabine/carboplatin or gemcitabine/carboplatin alone as follows: * Arm A: patients will receive 2 cycles of induction avelumab 10mg/kg every 2 weeks followed by 6 cycles of carboplatin/gemcitabine plus avelumab (carboplatin 5AUC day +1, gemcitabine 1000mg/m2 day +1 and +8 and avelumab 10mg/kg day +15) every 3 weeks followed by avelumab monotherapy 10mg/kg every 2 weeks until progressive disease or intolerance. * Arm B: patients will receive 6 cycles of carboplatin/gemcitabine (carboplatin 5AUC day +1, gemcitabine 1000mg/m2 day +1 and +8) every 3 weeks. Random assignment of treatment will be stratified by the presence or absence of visceral metastasis and ECOG \< 2 versus ECOG 2. All the patients enrolled in avelumab arm will receive avelumab monotherapy maintenance until disease progression or intolerable/unacceptable toxicity. Patients in the carboplatin-gemcitabine arm, will receive up to six cycles of treatment. Tumour evaluations will be scheduled every 6 weeks (±2 weeks) during carboplatin-gemcitabine treatment (in case of cycle delay this tumour evaluations every 6 weeks should be maintained to avoid any bias in the assessment of date of progression with appropriate imaging studies for response evaluation) and every 9 weeks thereafter until progressive disease (during this period, patients at arm A will be receiving avelumab maintenance treatment). Patients with disease progression during the treatment phase will be withdrawn from the study and will receive their treatment according to the investigator's judgment and monitored to evaluate OS. If a patient withdraws consent and refuses to receive more treatment, the patient must be followed up for survival. If a patient withdraws consent and refuses to continue in the study, the follow-up evaluations must be discontinued. If at the moment of end of study there would be any patient still on maintenance treatment with avelumab, Sponsor will have commitment to provide the study drug in case patient is having clinical benefit.

Conditions

• Metastatic Urothelial Cancer

Interventions

Type	Name	Description
COMBINATION_PRODUCT	avelumab 10mg/kg with carboplatin/gemcitabine	Dosage and schedule: * Avelumab 10mg/kg will be administered over 60 minutes in the experimental arm as follows: * Intravenously every 2 weeks for two cycles. * During carboplatin-gemcitabine treatment, on day +15 (carboplatin will be administered on day 1; gemcitabine on days 1 and 8), for six cycles. Intravenously every 2 weeks until progressive disease o intolerance. * Intravenously every 2 weeks until progressive disease or intolerance. * Carboplatin-gemcitabine will be administered for six cycles, every three weeks, with the following posology, according to the SmPC * Carboplatin 5AUC day +1. * Gemcitabine 1000mg/m2 day +1 and +8.
COMBINATION_PRODUCT	carboplatin/gemcitabine alone	•Carboplatin-gemcitabine will be administered for six cycles, every three weeks, with the following posology, according to the SmPC * Carboplatin 5AUC day +1. * Gemcitabine 1000mg/m2 day +1 and +8.

Timeline

• Start date: 2018-05-17
• Primary completion: 2022-08-31
• Completion: 2022-08-31
• First posted: 2018-01-04
• Last updated: 2023-10-18

Locations

15 sites across 1 country: Spain